Blood test detects breast cancer metastasis early

Circulating tumor DNA in the blood identified breast cancer metastases an average of 11 months before clinical detection, according to a new study published in EMBO Molecular Medicine (2015; doi:10.15252/emmm.201404913).

Although the chances of a breast cancer cure have increased in recent decades, if metastases occur, the disease remains essentially incurable. One reason for this could be that the metastases are detected late, after they have grown enough to cause symptoms or be seen on a radiological scan. If they could be found sooner, treating the new tumors might be possible. Research findings from Lund University in Sweden now provide new hope for a way of detecting metastases significantly earlier than is currently possible.

The discovery was made by a research team led by Lao Saal, MD, PhD, and is based on what is known as cell-free circulating DNA, which are small fragments of genetic material from different cells that circulate in the blood. It is normal to have low amounts of such DNA material in the blood, but in the case of diseases such as cancer, these amounts can increase. Furthermore, in cancer patients, the circulating DNA contains the genetic mutations that are specific to the tumor.

Lao Saal and his colleagues used previously gathered material from a breast cancer study that has been underway in Lund since 2002. The material contained samples from surgically removed tumors from patients with nonmetastatic disease as well as blood samples taken from the patients at regular intervals during the years in which they were followed up.

The tumor samples contained many genetic changes, which constituted a fingerprint specific to each tumor. Researchers then looked in the blood samples for circulating tumor DNA (ctDNA) with the same fingerprint. Although the study is fairly small and includes material from only 20 women, its results are striking.

"For 19 of the 20 women, the ctDNA in the blood samples gave a clear indication of how things would turn out. The women who never got a relapse had no detectable ctDNA, whereas all women who had tumor DNA in their blood eventually had symptomatic relapses that were diagnosed in the clinic", said Lao Saal.

The metastases were also reflected in the blood samples at an early stage. There it was possible to find signs of the new tumors many months before hospital investigations revealed that the patients had suffered a relapse.

"The circulating tumor DNA values in the blood samples identified the metastases on average 11 months before they were diagnosed by standard clinical procedures. In some cases, the blood test detected the metastasis 3 years earlier. If we could find the cancer recurrences that much earlier, we might be able to treat them more successfully," said Lao Saal.

The study must be followed by investigations with more participants, so that researchers can be sure that the results are sustainable. If they are, ctDNA testing could become a way of detecting breast cancer metastasis much earlier than is currently possible.